M. Manning, W. H. Sawyer and coworkers have published a series of papers describing various [1-(.beta.-mercapto-.beta.,.beta.-cyclopentamethylenepropionic acid)-4-valine]-arginine-vasopressin congeners which have antivasopressin activity. Representative of these are EPA No. 61,356, U.S. Pat. Nos. 4,367,225 and 4,399,125.
All of the Manning compounds have a tripeptide chain attached at unit 6 of the 6-unit dithio ring and are, of course, nonapeptides. The present compounds are distinguished over these by being des-Pro.sup.7 des-Gly.sup.9 vasopressins yet having substantial antagonist activity.
Also, a previously filed U.S. patent application, Ser. No. 467,117 filed Feb. 16, 1983, discloses certain octapeptide vasopressin congeners which have the 9-Gly unit deleted and which have potent VSP antagonist activity.
All of the previously disclosed compounds have structures which have an essential proline-like unit at position 7 of VSP. The compounds of this invention have no such unit in their structures and have substantial VSP antagonist of aquaretic activity.
In the description herein and in the claims, the nomenclature common in the art of peptide and vasopressin chemistry is used. When no configuration is noted, the amino acid unit is in the L, or naturally occuring, form. In certain structural formulas, the thio members of the Pap and Cys units are added for clarity.
Certain of the peptide art designations used herein are the following: Pap, .beta.-mercapto-.beta.,.beta.-cycloalkylenepropionic acid; Pmp, .beta.-mercapto-.beta.,.beta.-cyclopentamethylenepropionic acid; Abu, .beta.-aminobutyric acid; Chg, cyclohexylglycine; Cha, cyclohexylalanine; Pba, aminophenylbutyric acid, Gln, glutamic acid amide; Gly, glycine; Tyr, tyrosine; Phe, phenylalanine; Val, valine; Ile, isoleucine; Nle, norleucine; Leu, leucine; Ala, alanine; Lys, lysine; Arg, arginine; Asn, asparagine; Tos, tosylate; BHA, benzhydrylamine; DIEA, diisopropylethylamine; 4-MeBzl, 4-methylbenzyl; TFA, trifluoroacetic acid; DCC, dicyclohexylcarbodiimide; HBT, hydroxybenzotriazole; ACM, acetamidomethyl.